Long-term neuroprotection and neurorestoration by glial cell-derived neurotrophic factor microspheres for the treatment of parkinson's disease

BACKGROUND: Glial cell-derived neurotrophic factor is a survival factor for dopaminergic neurons and a promising candidate for the treatment of Parkinson's disease. However, the delivery issue of the protein to the brain still remains unsolved. Our aim was to investigate the effect of long-term...

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Autores: Garbayo, E. (Elisa)|||/items/c0fa35e4-82c5-44f7-b300-740027106dba, Ansorena-Artieda, E. (Eduardo)|||/items/eee6c2d6-f73a-48d3-a5f8-fe090b677c82, Lanciego-Pérez, J.L. (José Luis)|||/items/d2d4dbfe-4daf-4103-89ec-2ebf41b65cd1, Blanco-Prieto, M.J. (María José)|||/items/93e177db-635f-456f-b672-b79ef8befc40, Aymerich-Soler, M.S. (María Soledad)|||/items/f65ae32b-d1a8-4fa4-ba9f-b8b10241f470
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/20124
Acceso en línea:https://hdl.handle.net/10171/20124
Access Level:acceso abierto
Palabra clave:Parkinson’s disease
Glial cell-derived neurotrophic factor
Microspheres
Neurodegeneration
6-hydroxydopamine
Tyrosine hydroxylase
Descripción
Sumario:BACKGROUND: Glial cell-derived neurotrophic factor is a survival factor for dopaminergic neurons and a promising candidate for the treatment of Parkinson's disease. However, the delivery issue of the protein to the brain still remains unsolved. Our aim was to investigate the effect of long-term delivery of encapsulated glial cell-derived neurotrophic factor within microspheres. METHODS: A single dose of microspheres containing 2.5 μg of glial cell-derived neurotrophic factor was implanted intrastriatally in animals 2 weeks after a 6-hydroxydopamine lesion. RESULTS: The amphetamine test showed a complete behavioral recovery after 16 weeks of treatment, which was maintained until the end of the study (week 30). This effect was accompanied by an increase in dopaminergic striatal terminals and neuroprotection of dopaminergic neurons. CONCLUSIONS: The main achievement was the long-term neurorestoration in parkinsonian animals induced by encapsulated glial cell-derived neurotrophic factor, suggesting that microspheres may be considered as a means to deliver glial cell-derived neurotrophic factor for Parkinson's disease treatment. © 2011 Movement Disorder Society.